Programmed conversion of hypertrophic chondrocytes into osteoblasts and marrow adipocytes within zebrafish bones

  1. Dion Giovannone
  2. Sandeep Paul
  3. Simone Schindler
  4. Claire Arata
  5. D'Juan T Farmer
  6. Punam Patel
  7. Joanna Smeeton
  8. J Gage Crump  Is a corresponding author
  1. Keck School of Medicine of University of Southern California, United States

Abstract

Much of the vertebrate skeleton develops from cartilage templates that are progressively remodeled into bone. Lineage tracing studies in mouse suggest that chondrocytes within these templates persist and become osteoblasts, yet the underlying mechanisms of this process and whether chondrocytes can generate other derivatives remain unclear. We find that zebrafish cartilages undergo extensive remodeling and vascularization during juvenile stages to generate fat-filled bones. Growth plate chondrocytes marked by sox10 and col2a1a contribute to osteoblasts, marrow adipocytes, and mesenchymal cells within adult bones. At the edge of the hypertrophic zone, chondrocytes re-enter the cell cycle and express leptin receptor (lepr), suggesting conversion into progenitors. Further, mutation of matrix metalloproteinase 9 (mmp9) results in delayed growth plate remodeling and fewer marrow adipocytes. Our data support Mmp9-dependent growth plate remodeling and conversion of chondrocytes into osteoblasts and marrow adipocytes as conserved features of bony vertebrates.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Dion Giovannone

    Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Sandeep Paul

    Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2721-1874
  3. Simone Schindler

    Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Claire Arata

    Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. D'Juan T Farmer

    Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Punam Patel

    Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Joanna Smeeton

    Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. J Gage Crump

    Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, United States
    For correspondence
    gcrump@usc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3209-0026

Funding

National Institute of Dental and Craniofacial Research (R35 DE027550)

  • J Gage Crump

Burroughs Wellcome Fund (Postdoctoral Fellowship)

  • D'Juan T Farmer

National Institute of Dental and Craniofacial Research (F31 025549)

  • Dion Giovannone

National Institute of Dental and Craniofacial Research (K99 DE027218)

  • Joanna Smeeton

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#20771) of the University of Southern California.

Reviewing Editor

  1. Clifford J Rosen, Maine Medical Center Research Institute, United States

Publication history

  1. Received: October 10, 2018
  2. Accepted: February 13, 2019
  3. Accepted Manuscript published: February 20, 2019 (version 1)
  4. Version of Record published: March 4, 2019 (version 2)

Copyright

© 2019, Giovannone et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Dion Giovannone
  2. Sandeep Paul
  3. Simone Schindler
  4. Claire Arata
  5. D'Juan T Farmer
  6. Punam Patel
  7. Joanna Smeeton
  8. J Gage Crump
(2019)
Programmed conversion of hypertrophic chondrocytes into osteoblasts and marrow adipocytes within zebrafish bones
eLife 8:e42736.
https://doi.org/10.7554/eLife.42736

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